tbuckley/cabot-search huggingface dataset:
Abstract 13938: Metabolically Healthy Obese and Incident Coronary Heart Disease in Adult Cancer Survivors
Authors: Kyuwoong Kim
Journal: Circulation (2022)

Introduction: There is a paucity of data on the combined association of metabolic health status and obesity with coronary heart disease (CHD) in adult cancer survivors who are at excess risk of CHD associated with potentially harmful side effects from some cancer therapies. Long-term cardiovascular health among adult cancer survivors who are metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUN), and metabolically unhealthy obese (MUO) as compared to those who are metabolically healthy non-obese (MHN) remains uncertain. Hypothesis: The hypothesis of this study was that adult cancer survivors who are MHO, MUN, MUO would have higher risk of CHD as compared to those who are MHN. Methods: Data on metabolic health status and incident CHD among adult cancer survivors (n=2,336) were abstracted from the National Health Insurance Service-Health Screening Cohort, 2002-2019 along with information on confounding variables (sociodemographic factors, health status, health behavior, and family history of heart disease). Obesity was defined as body mass index≥25.0 kg/m 2 and the participants were considered metabolically unhealthy if they met more than three out of the five (fasting serum glucose, blood pressure, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol) criteria for worsened metabolic health. Cox proportional hazards model adjusted for the confounding variables was used to compute hazard ratios (HR) and 95% confidence intervals (95% CI) for incident CHD according to the metabolic health and obesity categories. Results: Among adult cancer survivors, those who are MHO (HR=2.80; 95% CI: 1.65-4.76), MUN (HR=2.58; 95%: 1.12-5.97), and MUO (HR=4.88; 95% CI: 2.27-10.5) had higher risk of incident CHD as compared to those who are MHN. Conclusions: Adult cancer survivors who are MHO should also be of a clinical concern. Excess body weight and metabolic health status should be concurrently managed to reduce the risk of developing CHD among adult cancer survivors.
Abstract 13862: Trends in Complication Rates Post-Transcatheter Aortic Valve Replacement
Authors: Anand Muthu Krishnan, George Zhang, Toishi Sharma, Frank Ittleman, Rony Lahoud
Journal: Circulation (2022)

Introduction: Transcatheter Aortic Valve Replacement (TAVR) is a mainstay of treatment for aortic valve stenosis for patients. It is unclear if this has resulted in a significant change in post-procedural complications over time. Hypothesis: We hypothesised a reduction in major complication rates across our study period given the improvement in delivery systems. Methods: This is a nationwide temporal trends study utilizing the 2016-2019 National In Patient Sample (NIS) registry. Patients who underwent TAVR including those with major procedural complications (i.e: need for transfusion or permanent pacemaker implantation [PPMI]) were identified. The trends in overall complication rate and individual complication rates between 2016 to 2019 were analysed. Multivariate model was built to predict the factors influencing complications. Results: Between 2016-2019, 217,110 patients underwent TAVR of which 12.6% had atleast one major complication. Proportion of complications decreased significantly across the study period(see Fig 1). Overall, females had a 10% higher complication rate (aOR 1.1, p=0.002) mainly driven by bleeding with over a 50% need for transfusion (aOR 1.57, p&lt;0.001) while having a 12% lower risk of PPMI (aOR 0.88, p=0.001). The Northeast region had a significantly higher complication rate driven by higher bleeding, with PPMI rate not differing geographically. Charlson comorbidity index (CCI) score was predictive of higher bleeding with a score of &gt;3 having over a threefold risk (aOR 3.4, p&lt;0.001). Conclusions: Our study shows that although there is a reduction in complication rate post-TAVR, the changes are uneven across different complications and population groups. More than 10% of patients were still experiencing a complication as recently as 2019. This could be a reflection of moving towards lower risk population, recent improvements in valve profile and implantation technique and a better understanding of predictors of PPMI.
Abstract 14039: The Cardioprotective and Anti-Inflammatory Effect of Inhaled Nitric Oxide During Fontan Surgery: A Prospective Randomized Study
Authors: Jacek Kolcz, Elzbieta Karnas, Ewa K ZUBA SURMA
Journal: Circulation (2022)

Introduction: Open heart surgery that requires cardiopulmonary by-pass (CPB) evokes tremendous stress and inflammatory responses, affecting postoperative organ function, morbidity, and mortality. Although part of this reaction triggers protective and anti-inflammatory phenomena, it is harmful, particularly in patients with single ventricle congenital heart defects during Fontan surgery. Unfortunately, there is no perfect anti-inflammatory and stress defence strategy despite decades of research. Hypothesis: This study aimed to investigate the influence of nitric oxide (NO) inhaled directly into the oxygenator during CPB on a proteome profile of inflammatory cytokines, metabolic response markers, heart and lung protection indicators, and the early clinical outcomes. Methods: The study involved 115 patients randomized to the Fontan-NO group, receiving NO inhalation (n=48) and the Fontan group, not receiving NO (n=49). Eighteen patients were excluded from the study. The clinical data were prospectively analyzed. Proteome profiler essays were used for repeated measurements of investigated analytes. Results: Fontan-NO patients had significantly lower levels of lactate (p=0.04) and glucose (p=0.02), lower pulmonary artery pressure (p=0.03) and catecholamine index (p=0.042), shorter ventilatory support time (p=0.03) and ICU stay (p=0.04). Plasma factors analysis has shown a significantly higher concentration of interleukin-10, tissue inhibitor of metalloproteinase, prolactin, and angiopoietin and a lower concentration of interleukin-6, interleukin-8, interleukin-1β, granulocyte-macrophage colony-stimulating factor, pentraxin, matrix metalloproteinase-8, troponin-I, CK-MB, and insulin in Fontan-NO group. Multiple regression analysis revealed the influence of Il-6 and Il-8 on respiratory support time and ICU stay and the relationship between catecholamine index, duration of effusions, and indicators of myocardial damage. Conclusions: NO inhaled into the oxygenator during CPB can alleviate the inflammatory response, improve myocardial and lung protection, and reduce metabolic stress in patients with a single ventricle undergoing Fontan surgery. The observed effects can influence short-term clinical outcomes.
Abstract 14194: Risk Factors of Hypokalemia and Hyperkalemia in Hypertensive Emergency
Authors: Jia Wei Tan, Jay Parekh, Kwabena Sefah Nketiah Sarpong, Sun-Joo Jang, Samdish Sethi, Lakshmi Polisetty, Arjun Gogna
Journal: Circulation (2022)

Introduction: Potassium disorders are common among hypertensive patients. There is a paucity of data on the prevalence and risk factors of dyskalemia in patients with hypertensive emergency. Hypothesis: We sought to investigate the prevalence and risk factors of potassium disorders in patients presenting with hypertensive emergency. Methods: A retrospective, cross-sectional study was employed by retrieving electronic medical records (EMR) of patients with a diagnosis of hypertensive emergency admitted from September 2016–December 2021 under Yale New Haven Health system. Hypertensive emergency patients were identified using the International Classification of Diseases, Tenth Edition (ICD-10) diagnosis. We selected patients who carried the diagnosis code of hypertensive emergency (I16.1) and at least 1 additional diagnosis for concurrent end organ damage (EOD). We manually examined all the electronic medical record (EMR) (n = 2664) to assure the correct establishment of diagnosis and removed 345 patients who are hypertensive urgency misclassified as hypertensive emergency. Hypokalemia is defined as serum potassium &lt;3.5 mg/dL and hyperkalemia is defined as &gt;5.5 mg/dL. Results: Among a total of 2,319 patients included in the study, 1,157(49.9%) were women and 1162(50.1%) were men. The mean age of the patients was 67.3 years. We have941(40.6%) African Americans, , 1048( 45.2%) Caucasian, and the rest of 240 (14.2%) are either Asians or unspecified. Average systolic blood pressure on presentation was 193 mmHg and average diastolic blood pressure was 106 mmHg. 143 (6.2%) patients had hyperkalemia and 260 (11.2%) patients had hypokalemia. After multivariable adjustment, older age, lower serum bicarbonate, elevated serum sodium and elevated serum creatinine were independently associated with hyperkalemia, and younger age, African American, higher serum bicarbonate, lower serum sodium, and lower serum creatinine were independently associated with hypokalemia. Conclusions: We identify a potential clinical phenotype of hypertensive emergency patients who present with potassium disorder. The risk for hypo- and hyperkalemia in hypertensive emergency can be stratified with common laboratory results and socio-demographic variable.
Abstract 13560: System Gene Regulatory Network-Based Drug Repurposing Combined With Preclinical Molecular Imaging Identifies Anti-Atherosclerotic Properties of Auranofin
Authors: Letizia Amadori, Claudia Calcagno, Ravneet Kaur, Peik Sean Chong, swathy sajja, Roza Shamailova, Sonum Naidu, Raphael Soler, Christopher Faries, Adam A Ghotbi, Ben Readhead, Joel Dudley, Zahi A Fayad, Johan Bjorkegren, Chiara Giannarelli
Journal: Circulation (2022)

Introduction: The identification of new treatments for atherosclerosis (ACVD), a common complex disease, is a daunting task because sets of genes, rather than individual genes, control cell functions. Using systems genetics, our team identified gene regulatory network (GRN42) that is active in the human atherosclerotic arterial wall and is involved in the regulation of foam cell formation. Hypothesis: A network-driven drug repurposing approach combined with rigorous preclinical validation will identify new uses for existing drugs to treat ACVD. Methods: We developed a GRN42-based computational drug repurposing pipeline to infer new uses for existing drugs. Selected compounds were screened by measuring their ability to inhibit foam cell formation in vitro using THP-1-derived macrophages. The in vivo efficacy was validated in ApoE-/- mice fed a western diet by histology and in atherosclerotic rabbits using histology and non-invasive 18 F-FDG PET-MR imaging. Results: 30 candidate compounds were predicted to influence the function of GRN42 and 5 were selected for in vitro screening based on their prediction scores (Figure 1A). As expected, vitamin D reduced cholesteryl esters accumulation in foam cells. Auranofin, and FDA-approved drug for rheumatoid arthritis reduced foam cell formation. As predicted methyl-fasudil had no effect, while nicardipine and flutamide increased foam cell formation (Figure 1B). Auranofin reduced plaque burden in ApoE-/- mice (Figure 1C) and in rabbits reduced lipid accumulation (Figure 1D) and inflammation shown as reduced 18 F-FDG uptake in the arterial wall (Figure 1E). Conclusions: Our results provide robust evidence that a GRN-based computational drug repurposing approach, when combined with robust preclinical validation using translational molecular imaging, can successfully identify new uses of existing drugs for the treatment of ACVD.
Abstract 13968: The Alteration in Hepatic Inner Mitochondrial Membrane Fusion Affects Lipoprotein Metabolism and Liver Fat Accumulation
Authors: Lorenzo Da Dalt, Annalisa Moregola, Patrizia Uboldi, Giuseppe Danilo Norata
Journal: Circulation (2022)

Introduction: in liver, mitochondria continuously undergo biogenesis, fusion, fission and mitophagy, and thus participate to the regulation of energy metabolism, calcium homeostasis and lipid metabolism. Hypothesis: test the role of selective deletion of a key protein involved in inner mitochondrial membrane fusion (OPA1) in hepatocytes on mitochondrial function and lipid metabolism. Methods: liver selective OPA-1 deficient mice (Opa1LKO) were generated by crossing OPA-1 flox/flox mice with albumin-CRE+ mice. Opa1LKO and OPA1 flox/flox (controls) mice were fed a high fat diet for 20 weeks and then in vivo metabolic responses, liver and fat characteristics and proteomic signature were profiled. Results: Opa1LKO mice fed with HFD display reduced weight and weight gain compared to controls. Opa1LKO presented a significant reduction in fasting glycaemia as well as improved glucose tolerance and insulin tolerance compared to Opa1 WT. Moreover, plasma cholesterol levels and cholesterol distribution in lipoprotein fractions was reduced in Opa1LKO compared to Opa1 WT and the same was true for triglycerides. In vivo metabolic cages experiments revealed a reduced oxygen consumption and increased respiratory exchange rate in Opa1LKO compared to Opa1WT.Liver OPA1 deficiency limited lipid accumulation in the liver compared to Opa1 WT. Moreover, the liver from Opa1LKO mice presented an increased prevalence of smaller LD compared to Opa1 WT suggesting that diminished lipid accumulation and smaller LDs could be associated to changes in liver morphology and structure. In parallel Opa1LKO presented smaller adipocytes both in VAT and in SCAT compared to Opa1 WT. Interestingly, proteins involved in bile acids synthesis and transport were reduced in Opa1LKO liver compared to Opa1 WT, in parallel also proteins involved in lipoproteins uptake, lipoprotein synthesis (MTTP) and apolipoproteins (apoA-I, apoA2, apoB) were reduced. Conclusion: Our data suggest that the impairment of mitochondrial fusion could rewire liver metabolism and leads to cholestasis. This could be the consequence of altered bile acid synthesis, due to impaired mitochondrial activity, which results in reduced lipid absorption and limited liver lipid accumulation under HFD conditions.
Abstract 14001: Evaluation and Treatment of Patients With Low Ejection Fraction and Positive Troponin
Authors: Mohammad Hamza, Andrew Castellano, Majd Al-Ahmad, John Stone, Hafiza Hareem Waqar, Jeannette Mullins, Mikhail Torosoff, Neil Yager
Journal: Circulation (2022)

Introduction: Patients with decreased LV ejection fraction (LVEF) presenting with elevated troponin incur high in-patient and follow-up mortality. Despite guidelines, testing for CAD and guideline-directed therapy in such patients has not been consistently utilized. To better understand this issue, we investigated hospital practice patterns in this vulnerable population. Methods: We conducted a tertiary single-center study of consecutive in-patients with abnormal troponin results on testing performed for clinical indications as requested by the treating physician. The study cohort included 432 patients, 67 +/- 14 years old with HTN in 75%, DM in 38%, smoking in 51%, dyslipidemia in 64%, family history of CAD in 28% and personal history of CAD or equivalent in 46%. Among them, 412 patients underwent echocardiographic LVEF assessment. Patients were then stratified according to the LVEF. The use of both ischemic evaluation and evidence-based medical therapy were compared. Hospital and long-term outcomes were analyzed. Results: Hospital mortality was 51/432 (11.8%) and during 28.1+/-13.8 months of follow-up additional 82/432 (18.9%) patients expired. Ischemia evaluation (both cardiac catheterization and non-invasive) was underutilized across all subgroups, including patients with decreased LVEF. Regarding guideline-directed medical therapy, only beta-blocker therapy was consistently utilized. Afterload reduction therapies such as angiotensin convertase enzyme inhibitors, angiotensin II receptor blockers, neprilysin inhibitors, hydralazine and nitrates were significantly underutilized. Statins and mineralocorticoid receptor blockers were also significantly underused (Table). Conclusions: Despite increased mortality, there continues to be room for improvement in the utilization of diagnostic evaluation and application of evidence-based therapy and in patients admitted with elevated cardiac biomarkers.
Abstract 13480: The Association Between Exercise Intolerance and Diagnostic Scores for Suspected Heart Failure With Preserved Ejection Fraction Patients
Authors: Chan Joo Lee, MINJAE YOON, Jaewon Oh, Seok-min Kang
Journal: Circulation (2022)

Introduction: The newly proposed HFA-PEFF and H 2 FPEF scores have been used in diagnosing heart failure with preserved ejection fraction (HFpEF). Hypothesis: We investigated the association between these scores and exercise intolerance in suspected HFpEF patients. Methods: We analyzed 2,031 patients with one more symptom of HF who underwent echocardiography, cardiopulmonary exercise test, and measurement of NT-proBNP between 2012 and 2021 at a single tertiary center. After excluding the patients with LVEF &lt;50% or apparent cause of HF symptoms other than HFpEF, 1,032 patients with suspected HFpEF were enrolled in calculating the HFA-PEFF and H 2 FPEF scores to estimate the probability of HFpEF. Results: Patients (mean age 61 years old, 63.9% female, 6.7% atrial fibrillation) were stratified according to HFA-PEFF scores [0-1 (low, n=219), 2-4 (intermediate, n=590), or 5-6 (high, n=223)] and H 2 FPEF scores [0-1 (low, n=378), 2-5 (intermediate, n=605), or 6-9 (high, n=49)]. Cohen’s weighted kappa coefficient for agreement of both scores risk category was 0.47. The mean peak VO 2 was 29.4, 24.6, 20.6 (p&lt;0.001), and 28.1, 23.1, 19.6 (p&lt;0.001) ml/kg/min in the low, intermediate, and high-risk category according to HFA-PEFF and H 2 FPEF scores, respectively. Also, peak VO 2 was correlated with the HFA-PEFF and H 2 FPEF scores (r=-0.454, p&lt;0.001; r=-0.463, p&lt;0.001). The HFA-PEFF and H 2 FPEF had the predictive value of low peak VO2 (&lt;20 ml/kg/min) with AUC 0.708 and 0.731, respectively. Conclusions: HFA-PEFF and H 2 FPEF scores were associated with exercise capacity. This association supports the clinical usefulness of HFA-PEFF and H 2 FPEF scores as an indicator of exercise intolerance in HFpEF patients.
Abstract 13684: Comparison Between Men and Women With Severe Obesity for Risk of Adverse Outcomes of Myocardial Ischemia: An Exercise Stress Echocardiographic Study
Authors: Errol Moras, Kruti Gandhi, Joseph Elias, David Meister, Maria Pena, Christopher Perez Lizardo, Brissete Mancero, GaHee kim, Elizabeth Zipf, Loba Alam, Swiri Konje, Alaa M Omar, Edgar Argulian
Journal: Circulation (2022)

Background: Obesity and sex have a complex relationship with myocardial ischemia. We explored the association of sex and severe obesity with adverse cardiovascular outcomes in patients with ischemic exercise stress echocardiography (EXE). Methods: We retrospectively studied 142 patients with ischemic ExE [Age: 65±11 years, 70(49%) women, EF: 57±8%, body mass index (BMI): 28±6 kg/m 2 ]. Severe obesity (BMI&gt;35 kg/m 2 ) occured in 48 (34%) patients. Patients were stratified based on obesity and sex (4 groups, women, and men with and without severe obesity), followed for median of 1.5 years, and compared for clinical, exercise variables and occurrence of composite outcomes (death, acute coronary syndrome, cardiac hospitalization and repeat ischemia testing). Results: In our study, 28(20%) women and 20(14%) men had severe obesity, and 42(29%) women and 52(37%) men had no severe obesity. Groups were not different for age, risk factors, exercise characteristics, and resting LV function. Outcomes occurred in 85(60%) patients and were more prevalent in women with severe obesity compared to women without or men with or without severe obesity [21(75%), 17(40%), 11(55%), and 35(67%), p=0.014]. Sex and severe obesity did not predict outcomes in isolation [HR: 1.13 (95%CI:0.74 to 1.73), 1.48 (95%CI:0.95 to 2.3), respectively, figure 1A, B]. Survival analysis showed that women without severe obesity were at lowest risk, men were at similarly elevated risk irrespective of severe obesity, and women with severe obesity were at highest risk for composite outcomes [p=0.037, figure 1C, HR: 2.5 (95% CI: 1.3 to 4.8)]. After adjusting for clinical, exercise, and echocardiographic variables, women with severe obesity remained at high-risk [HR: 2.2, (95% CI: 1.06 to 4.36)]. Conclusion: In patients with ischemic ExE, women with severe obesity are at higher risk for adverse cardiac outcomes. Future studies are needed to understand the pathophysiologic mechanisms underlying this association.
Abstract 14112: " <i>Leave My Tongue Alone</i> :" Is the Myth of Tongue Swallowing Still Preventing Proper Cardiopulmonary Resuscitation Efforts of Athletes With Cardiac Arrest?
Authors: Dana Viskin
Journal: Circulation (2022)

Introduction: In 2017, we reported that during cardiac arrest (CA) events of athletes caught on video, the initial response of fellow teammates and paramedical personnel, is incorrect and disturbing: An attempt to prevent and/or relief "tongue swallowing" takes precedent over chest compression. We aimed to see if our report had any impact on the proper resuscitation of athletes. Methods: We continued our internet search for events of CA or transient loss of consciousness (LOC) severe enough to prompt resuscitation. For each video, we focused on the resuscitation maneuvers performed by fellow athletes. In addition, we reviewed the news coverage of each event, to learn how the resuscitation efforts are described in social media. Results: We expanded our original 29-video-collection to a total of 42 videos and 1 news article, showing athletes collapsing with CA (n=33) or LOC prompting resuscitation (n=10). The athletes with witnessed CA had a mean age of 25 + 4 years and all but one were male. The first intervention was visible in 37 videos and in 83% it was an obvious attempt to prevent "tongue swallowing.” Chest compressions were applied to only 33% of athletes. Media coverage, in 34 lay press articles, portrayed this wrong response as “heroic” in 6 cases. In the rest, the wrong resuscitation maneuvers were neither criticized nor questioned. The phrase “preventing tongue swallowing” appears in 3 articles, all highly publicized (BBC, ESPN etc). When an athlete did not survive following these wrong cardiopulmonary resuscitation manoeuvres, the lay media ignored the erroneous resuscitation. Conclusion The lay-media coverage of CA events of athletes portrays a disturbing reality in which wrong actions by first responders, including the prevention of tongue swallowing, are deemed heroic, while the necessary criticism of these actions is absent.